摘要
目的探讨出生后镧暴露对大鼠海马基质金属蛋白酶–9(MMP–9)蛋白和mRNA表达水平影响。方法将Wistar孕鼠随机分为对照组和低、中、高剂量染镧组,自孕鼠分娩至仔鼠断乳后1个月通过自由饮水染镧。采用Western blot法检测仔鼠海马MMP–2和MMP–9蛋白表达,Real-Time PCR法检测仔鼠海马MMP–2/9和Timp–2/1mRNA表达。结果与对照组比较,中、高剂量染镧组仔鼠海马MMP–9蛋白表达水平[分别为(0.172±0.017)、(0.236±0.022)]、mRNA表达水平[分别为(1.267±0.102)、(1.456±0.081)]均显著升高(P<0.05)。与对照组比较,高剂量染镧组仔鼠海马Timp-1 mRNA表达水平(0.784±0.034)显著降低(P<0.05)。结论镧可上调仔鼠海马MMP–9蛋白和mRNA表达,下调Timp–1 mRNA表达,诱导MMP–9活化进而降解紧密连接蛋白,致使血脑屏障破坏。
Objective To observe the effect of postnatal lanthanum exposure on protein and mRNA expression of matrix metalloproteinase-9 （MMP-9） in hippocampus of rats.Methods Forty pregnant Wistar rats were randomly divided into a control group and low-, moderate-, and high-dose lanthanum groups and then their offspring were exposed to lanthanum of different concentration （0.25%, 0.50%, and 1.00%） through drinking water during lactation until one month after delactation. MMP-2 and MMP-9 protein expression in hippocampus were detected with Western blot, while MMP-2/9 and tissue inhibitors of metalloproteinase （Timp 2/1） mRNA levels were measured with real-time PCR.Results In comparison with those of the control group, significantly increased MMP-9 protein expression （0.172 ± 0.017 and 0.236 ± 0.022） and mRNA expression （1.267 ± 0.102 and 1.456 ± 0.081） were detected in offspring rats＇ hippocampuses of the moderate- and high-dose lanthanum groups （both P 〈 0.05）; moreover, a significant decrease in Timp1 mRNA expression （0.784 ± 0.034） was observed in hippocampuses of the offspring rats with high-dose lanthanum exposure.Conclusion Early postnatal period lanthanum exposure up-regulates protein and mRNA expression of MMP-9, but down-regulates Timp1 mRNA expression in hippocampus of offspring rats, resulting in blood-brain barrier damage due to the activation of MMP-9 and subcequent degradation of tight junction proteins.
出处
《中国公共卫生》
CAS
CSCD
北大核心
2018年第1期60-62,共3页
Chinese Journal of Public Health
基金
国家自然科学基金(81502837)
辽宁省科技厅基金项目(2015020367)
